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Biomedical subjects

J A Murray

Publications and source records attributed to J A Murray.

At least 37 records · Page 2Linked to original sources

Use of montelukast as steroid-sparing agent for recurrent eosinophilic gastroenteritis.

Patients with eosinophilic gastroenteritis generally respond well to corticosteroids but relapses are common. Patients with relapsing disease are usually placed on long-term low-dose prednisone or immunosuppressive therapy. Here we reported on a patient with severe steroid-dependent eosinophilic gastroenteritis who was able to successfully taper off steroids and maintain remission after starting montelukast, a leukotriene receptor antagonist. To our knowledge, this is the first use of montelukast as a steroid sparing agent for eosinophilic gastroenteritis.

Acetates↗

Diagnostic approach to a patient with suspected celiac disease: a cost analysis.

Serological testing is an important tool in the diagnostic work-up of suspected celiac disease. Our aim was to apply a decision analysis model to compare the costs of serological testing versus small bowel biopsy in the diagnostic work-up of celiac disease. A cost-minimization approach was employed. A decision analysis model with three diagnostic arms was designed using Data Version 3.5: anti-gliadin antibody versus endomysial antibody versus small bowel biopsy. Response to gluten-free diet was considered diagnostic of celiac disease; lack of response prompted a small bowel biopsy to definitively exclude celiac disease. Baseline probabilities were varied using sensitivity analysis. Sensitivity analysis revealed that the endomysial antibody strategy was least costly, provided the prevalence of celiac disease was less than 42%; above this anti-gliadin antibody became the most economical option. In conclusion, initial screening with endomysial antibody is the least costly strategy for diagnosing celiac disease in a low risk population. Antigliadin antibody becomes the cheaper strategy for higher risk populations.

Biopsy↗

Phytodetoxification of TNT by transgenic plants expressing a bacterial nitroreductase.

There is major international concern over the wide-scale contamination of soil and associated ground water by persistent explosives residues. 2,4,6-Trinitrotoluene (TNT) is one of the most recalcitrant and toxic of all the military explosives. The lack of affordable and effective cleanup technologies for explosives contamination requires the development of better processes. Significant effort has recently been directed toward the use of plants to extract and detoxify TNT. To explore the possibility of overcoming the high phytotoxic effects of TNT, we expressed bacterial nitroreductase in tobacco plants. Nitroreductase catalyzes the reduction of TNT to hydroxyaminodinitrotoluene (HADNT), which is subsequently reduced to aminodinitrotoluene derivatives (ADNTs). Transgenic plants expressing nitroreductase show a striking increase in ability to tolerate, take up, and detoxify TNT. Our work suggests that expression of nitroreductase (NR) in plants suitable for phytoremediation could facilitate the effective cleanup of sites contaminated with high levels of explosives.

Bacteria↗

Is there a role for gastric accommodation and satiety in asymptomatic obese people?

OBJECTIVE: The relationships of gastric accommodation and satiety in moderately obese individuals are unclear. We hypothesized that obese people had increased gastric accommodation and reduced postprandial satiety. The objective of this study was to compare gastric accommodation and satiety between obese and non-obese asymptomatic subjects. RESEARCH METHODS AND PROCEDURES: In 13 obese (body mass index [BMI] > or = 30 kg/m(2); mean BMI, 37.0 +/- 4.9 kg/m(2)) and 19 non-obese control subjects (BMI < 30 kg/m(2); mean BMI, 26.2 +/- 2.9 kg/m(2)), we used single photon emission computed tomography to measure fasting and postprandial gastric volumes and expressed the accommodation response as the ratio of postprandial/fasting volumes. The satiety test measured maximum tolerable volume of ingestion of liquid nutrient meal (Ensure) and symptoms 30 minutes after cessation of ingestion. RESULTS: Total fasting and postprandial gastric volumes and the ratio of postprandial/fasting gastric volume were not different between asymptomatic obese and control subjects. However, the fasting volume of the distal stomach was greater in obese than in control subjects. Maximum tolerable volume of ingested Ensure and aggregate symptom score 30 minutes later were also not different between obese and control subjects. DISCUSSION: Asymptomatic obese individuals (within the BMI range of 32.6 to 48 kg/m(2)) did not show either increased postprandial gastric accommodation or reduced satiety. These data suggest that gastric accommodation is unlikely to provide an important contribution to development of moderate obesity.

Adult↗

Spherocytosis preceding the development of myelodysplasia.

We report two patients with prominent spherocytosis in the peripheral blood who later went on to develop myelodysplasia. There was no evidence of a myelodysplastic syndrome at the time of presentation. Morphological abnormalities of the peripheral blood along with possible explanations of spherocytosis are discussed.

Aged↗

Low incidence of Helicobacter pylori infection in patients with duodenal ulcer and chronic liver disease.

BACKGROUND: Duodenal ulcer (DU) is a common problem in patients with chronic liver disease (CLD) and with inadequate response to H2 receptor antagonists. Omeprazole might be more effective. In DU-CLD patients, Helicobacter pylori prevalence is low. Nitric oxide is increased in gastric mucosa in cirrhosis. Oxygen-free radicals have a role in gastric inflammation and are abnormal in CLD. Nitrotyrosine is a marker of nitric oxide and oxygen-free radical toxic mucosal reaction. METHODS: Sixty-nine patients were divided into 2 groups: control (26 patients with DU) and CLD groups (43 patients, DU-CLD). Omeprazole was given (40 mg/day) for 2 or 4 weeks. Symptoms and endoscopy findings were recorded before and after treatment. Antral biopsy specimens were stained for H. pylori and nitrotyrosine. RESULTS: Clinical features of DU are similar in patients with and without CLD. The main presentation was epigastric pain (70%) and bleeding (23%). Healing rate with omeprazole was higher in DU-CLD patients (90.7%) than in controls (80.8%). H. pylori was much lower in DU-CLD patients (51.2%) than controls (96.2%). Nitrotyrosine staining was negative in normal controls (0%) and positive in control-DU (100%), CLD-H. pylori positive (81%), and CLD-H. pylori negative (91%) cases. CONCLUSIONS: DU in patients with CLD is not different clinically from those without CLD. Omeprazole effectively and safely treats DU in CLD. Nitric oxide and free oxygen radicals may result in gastric mucosal changes in CLD similar to that caused by H. pylori.

Adult↗

Selective nonoperative management in 1,856 patients with abdominal gunshot wounds: should routine laparotomy still be the standard of care?

OBJECTIVE: To evaluate the safety of a policy of selective nonoperative management (SNOM) in patients with abdominal gunshot wounds. SUMMARY BACKGROUND DATA: Selective nonoperative management is practiced extensively in stab wounds and blunt abdominal trauma, but routine laparotomy is still the standard of care in abdominal gunshot wounds. METHODS: The authors reviewed the medical records of 1,856 patients with abdominal gunshot wounds (1,405 anterior, 451 posterior) admitted during an 8-year period in a busy academic level 1 trauma center and managed by SNOM. According to this policy, patients who did not have peritonitis, were hemodynamically stable, and had a reliable clinical examination were observed. RESULTS: Initially, 792 (42%) patients (34% of patients with anterior and 68% with posterior abdominal gunshot wounds) were selected for nonoperative management. During observation 80 (4%) patients developed symptoms and required a delayed laparotomy, which revealed organ injuries requiring repair in 57. Five (0.3%) patients suffered complications potentially related to the delay in laparotomy, which were managed successfully. Seven hundred twelve (38%) patients were successfully managed without an operation. The rate of unnecessary laparotomy was 14% among operated patients (or 9% among all patients). If patients were managed by routine laparotomy, the unnecessary laparotomy rate would have been 47% (39% for anterior and 74% for posterior abdominal gunshot wounds). Compared with patients with unnecessary laparotomy, patients managed without surgery had significantly shorter hospital stays and lower hospital charges. By maintaining a policy of SNOM instead of routine laparotomy, a total of 3,560 hospital days and $9,555,752 in hospital charges were saved over the period of the study. CONCLUSION: Selective nonoperative management is a safe method for managing patients with abdominal gunshot wounds in a level 1 trauma center with an in-house trauma team. It reduces significantly the rate of unnecessary laparotomy and hospital charges.

Abdominal Injuries↗

Penetrating colon injuries requiring resection: diversion or primary anastomosis? An AAST prospective multicenter study.

BACKGROUND: The management of colon injuries that require resection is an unresolved issue because the existing practices are derived mainly from class III evidence. Because of the inability of any single trauma center to accumulate enough cases for meaningful statistical analysis, a multicenter prospective study was performed to compare primary anastomosis with diversion and identify the risk factors for colon-related abdominal complications. METHODS: This was a prospective study from 19 trauma centers and included patients with colon resection because of penetrating trauma, who survived at least 72 hours. Multivariate logistic regression analysis was used to compare outcomes in patients with primary anastomosis or diversion and identify independent risk factors for the development of abdominal complications. RESULTS: Two hundred ninety-seven patients fulfilled the criteria for inclusion and analysis. Overall, 197 patients (66.3%) were managed by primary anastomosis and 100 (33.7%) by diversion. The overall colon-related mortality was 1.3% (four deaths in the diversion group, no deaths in the primary anastomosis group, p = 0.012). Colon-related abdominal complications occurred in 24% of all patients (primary repair, 22%; diversion, 27%; p = 0.373). Multivariate analysis including all potential risk factors with p values < 0.2 identified three independent risk factors for abdominal complications: severe fecal contamination, transfusion of > or = 4 units of blood within the first 24 hours, and single-agent antibiotic prophylaxis. The type of colon management was not found to be a risk factor. Comparison of primary anastomosis with diversion using multivariate analysis adjusting for the above three identified risk factors or the risk factors previously described in the literature (shock at admission, delay > 6 hours to operating room, penetrating abdominal trauma index > 25, severe fecal contamination, and transfusion of > 6 units blood) showed no statistically significant difference in outcome. Similarly, multivariate analysis and comparison of the two methods of colon management in high-risk patients showed no difference in outcome. CONCLUSION: The surgical method of colon management after resection for penetrating trauma does not affect the incidence of abdominal complications, irrespective of associated risk factors. Severe fecal contamination, transfusion of > or = 4 units of blood within the first 24 hours, and single-agent antibiotic prophylaxis are independent risk factors for abdominal complications. In view of these findings, the reduced quality of life, and the need for a subsequent operation in colostomy patients, primary anastomosis should be considered in all such patients.

Adult↗

Old age as a criterion for trauma team activation.

BACKGROUND: Elderly trauma patients have been shown to have a worse prognosis than young patients. Age alone is not a criterion for trauma team activation (TTA). In the present study, we evaluated the role of age > or = 70 years as a criterion for TTA. METHODS: The present study was a trauma registry study that included injured patients 70 years of age or older. Patients who died in hospital, were admitted to the intensive care unit (ICU) within 24 hours, or had a non-orthopedic operation were assumed to benefit from TTA. RESULTS: During a 7.5-year period, 883 elderly (> or = 70 years) trauma patients meeting trauma center criteria were admitted to our center. Overall, 223 patients (25%) met at least one of the standard TTA criteria. The mortality in this group was 50%, the ICU admission rate was 39%, and a non-orthopedic operation was required in 35%. The remaining 660 patients (75%) did not meet standard TTA criteria. The mortality was 16%, the need for ICU admission was 24%, and non-orthopedic operations were required in 19%. Sixty-three percent of patients with severe injuries (Injury Severity Score > 15) and 25% of patients with critical injuries (Injury Severity Score > 30) did not have any of the standard hemodynamic criteria for TTA. CONCLUSION: Elderly trauma patients have a high mortality, even with fairly minor or moderately severe injuries. A significant number of elderly patients with severe injuries do not meet the standard criteria for TTA. It is suggested that age > or = 70 years alone should be a criterion for TTA.

Age Factors↗

Cell cycle regulation of cyclin-dependent kinases in tobacco cultivar Bright Yellow-2 cells.

Plants possess two major classes of cyclin-dependent kinases (CDK) with cyclin-binding motifs PSTAIRE (CDK-a) and PPTA/TLRE (CDK-b). Tobacco (Nicotiana tabacum L. cv Bright Yellow-2) cells are the most highly synchronizable plant culture, but no detailed analysis of CDK activities has been reported in this system. Here we describe isolation of new PPTALRE CDKs (Nicta;CdkB1) from Bright Yellow-2 cells and present detailed analysis of the mRNA, protein and kinase activity levels of CdkB1, and the PSTAIRE CDKA during the growth and cell cycles. CdkA and CdkB1 transcripts are more abundant in exponential than in stationary phase cells, but the two genes show strikingly different regulation during the cell cycle. CdkA mRNA and protein accumulate during G1 in cells re-entering the cell cycle, and immunoprecipitated histone H1 kinase activity increases at the G1/S boundary. Aphidicolin synchronized cells show the highest CDKA-associated histone H1 kinase activity during S-G2 phases, although CdkA mRNA and protein levels are not significantly regulated. In contrast, CdkB1 transcripts are present at very low levels until S phase and CDKB1 protein and kinase activity is almost undetectable in G1. CdkB1 mRNA accumulates through S until M phase and its associated kinase activity peaks at the G2/M boundary, confirming that transcription of PPTALRE CDKs is cell cycle regulated. We suggest that CDKA kinase activity likely plays roles at the G1/S phase boundary, during S phase, and at the G2/M phase transition, and that CDKB1 kinase activity is present only at G2/M.

CDC2 Protein Kinase↗

Cigarette smoking and celiac sprue: a case-control study.

OBJECTIVE: Environmental factors other than gliadin exposure and certain HLA haplotypes may play a role in the pathogenesis of celiac disease. Previous studies have suggested a strong inverse relationship between cigarette smoking and celiac disease. We sought to determine the relationship between celiac disease and cigarette smoking in our patient population. METHODS: All newly diagnosed adults with biopsy-proven celiac disease evaluated at Mayo Clinic Rochester between January 1, 1993, and June 30, 1998, were identified. Three clinic patients who were matched to each case on geographical area of residence, age, gender, and calendar year of visit served as controls. Smoking information was obtained from a standard medical questionnaire that was completed by all clinic patients at the time of registration. The adjusted odds ratio for celiac disease in current and former smokers relative to nonsmokers was estimated with a matched three-to-one conditional logistic regression model. RESULTS: A total of 82 adults with biopsy-proven celiac disease were identified. At the time of diagnosis, the proportion of current smokers was 10% in cases and 10% in controls, yielding an adjusted odds ratio of 1.5 (95% CI = 0.5-4.3). In all, 34% of cases were former smokers versus 28% of controls, yielding an odds ratio of 1.6 (95% CI = 0.8-3.2). CONCLUSION: This case-control study was unable to detect an association between cigarette smoking and celiac disease.

Adult↗

Noninvasive measurement of gastric accommodation in patients with idiopathic nonulcer dyspepsia.

OBJECTIVES: Postprandial symptoms are associated with impaired postprandial gastric accommodation. The aims of this study were to apply a noninvasive method to measure accommodation of the entire stomach in healthy subjects and in patients with idiopathic dyspeptic symptoms, and to assess the frequency of abnormal gastric accommodation and emptying of solids in these patients. METHODS: In 20 healthy volunteers and 32 tertiary referral patients, we used i.v. 99mTc-single photon emission computed tomography (SPECT) to measure fasting and postprandial gastric volumes; we expressed the volume response to feeding ("accommodation") as the change in gastric volume and the ratio of postprandial/fasting volumes. The stomach was identified in transaxial SPECT tomographic images using a semiautomated, intensity-based extraction algorithm. Whole gastric volumes were measured using AnalyzeAVW software. Gastric emptying in patients was measured by scintigraphy. We also assessed dyspeptic symptoms and the association with normal or reduced accommodation. RESULTS: SPECT imaging detects the postprandial change in gastric volume ("accommodation") in health and disease. Among healthy subjects (eight men, 12 women), the postprandial/fasting gastric volume ratio was 4.9+/-1.7 (mean +/- SD; fifth through 95th percentiles 3-8, median 4.6). Thirteen (41%) patients with idiopathic nonulcer dyspepsia had reduced postprandial "accommodation." Gastric emptying was fast in four (13%), normal in 25 (78%), and slow in three (9%) patients. Both tests were normal in 50% of patients. Weight loss of >10 pounds tended to be more frequently observed in those with reduced "accommodation" (62% vs 32%, p = 0.09). CONCLUSIONS: SPECT imaging noninvasively measures fasting and postprandial gastric volumes in humans. Half the patients with idiopathic nonulcer dyspepsia had impaired gastric accommodation or emptying. Reduced gastric "accommodation" was observed in 41% of a group with idiopathic nonulcer dyspepsia. Abnormal gastric emptying is less frequent (22%).

Adult↗

Diagnosing gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a common condition with a variety of clinical manifestations and potentially serious complications. This article reviews available methods for diagnosing GERD. A clinical history of the classic symptoms of GERD, heartburn or acid regurgitation, is sensitive enough to establish the diagnosis in patients without other complications. Esophagogastroduodenoscopy is the best way to evaluate suspected complications of GERD, but endoscopic findings are insensitive for the presence of pathological reflux, and therefore they cannot reliably exclude GERD. The "gold standard" study for confirming or excluding the presence of abnormal gastroesophageal reflux is the 24-hour ambulatory esophageal pH monitoring test, and this study should be used for the evaluation of refractory symptoms and extraesophageal manifestations of GERD. A formal acid-suppression test is helpful in the evaluation of the atypical GERD symptom of noncardiac chest pain. Optimal use of currently available tests for GERD may allow for more efficient diagnosis and better characterization of the pathological manifestations associated with GERD.

Diagnostic Techniques, Digestive System↗

The Arabidopsis D-type cyclins CycD2 and CycD3 both interact in vivo with the PSTAIRE cyclin-dependent kinase Cdc2a but are differentially controlled.

D-type cyclins (CycD) play key roles in linking the Arabidopsis cell cycle to extracellular and developmental signals, but little is known of their regulation at the post-transcriptional level or of their cyclin-dependent kinase (CDK) partners. Using new antisera to CycD2 and CycD3, we demonstrate that the CDK partner of these Arabidopsis cyclins is the PSTAIRE-containing CDK Cdc2a. Previous analysis has shown that transcript levels of CycD2 and CycD3 are regulated in response to sucrose levels and that both their mRNA levels and kinase activity are induced with different kinetics during the G(1) phase of cells reentering the division cycle from quiescence. Here we analyze the protein levels and kinase activity of CycD2 and CycD3. We show that CycD3 protein and kinase activity parallel the abundance of its mRNA and that CycD3 protein is rapidly lost from cells in stationary phase or following sucrose removal. In contrast to both CycD3 and the regulation of its own mRNA levels, CycD2 protein is present at constant levels. CycD2 kinase activity is regulated by sequestration of CycD2 protein in a form inaccessible to immunoprecipitation and probably not complexed to Cdc2a.

Arabidopsis↗

Computer-assisted visualizations of neural networks: expanding the field of view using seamless confocal montaging.

Microscopic analysis of anatomic relationships within the neural networks of adult and developing tissues often requires sampling large spatial regions of neuronal architecture. To accomplish this, there are two common imaging approaches: (1) image the entire area at once with low spatial resolution; or (2) image small sections at higher magnification/resolution and then join the sections back together by mosaic reconstruction (photomontaging). Low magnification imaging is relatively rapid to perform, resulting in a visualization that encompasses a large field of view with an extended depth of field. However, for fluorescence microscopy, low magnification visualizations are often plagued by poor spatial resolution. High magnification imaging possesses superior spatial resolution, but it produces an image with limited depth of field. When creating a larger field of view, the final image is also fragmented at the boundaries where multiple images are stitched together. Using confocal microscopy as well as features of common image processing programs, we outline a new method to transform individual, spatially contiguous z-series into a montage with a seamless field of view and an extended depth of field. In addition, we show that the manual alignment of images our method requires does not introduce significant errors into the final image. We illustrate our method for visualizing neural networks using tissues from the adult gastropod mollusc, Tritonia diomedea, and the developing zebrafish, Danio rerio.

Animals↗

Cyclin D control of growth rate in plants.

The mechanisms by which plants modulate their growth rate in response to environmental and developmental conditions are unknown, but are presumed to involve specialized regions called meristems where cell division is concentrated. The possible role of cell division in influencing meristem activity and overall plant growth rate is controversial, with a prevailing view that cell division is secondary to higher order meristem controls. Here we show that a reduction in the length of the cell-cycle G1 phase and faster cell cycling occur when the rate of cell division in transgenic tobacco plants is increased by the plant D-type cyclin CycD2 (ref. 8). The plants have normal cell and meristem sizes, but elevated overall growth rates, an increased rate of leaf initiation and accelerated development in all stages from seedling to maturity. We conclude that cell division is a principal determinant of meristem activity and overall growth rate, and propose that modulation of plant growth rate is achieved through regulation of G1.

Arabidopsis↗

Nonoperative management of splenic injuries: have we gone too far?

HYPOTHESIS: Patients with severe blunt injuries to the spleen have a high likelihood of failing nonoperative management of splenic injuries (NOMSI). DESIGN: Review of medical records, helical computed tomographic imaging data, and trauma registry data. SETTING: Academic level I trauma center at a large county hospital. PATIENTS: A total of 105 patients with blunt trauma to the spleen, admitted between January 1995 and December 1998, who survived more than 48 hours and had complete records. Of these patients, 53 (56%) were selected for NOMSI. The splenic injury was graded by the Organ Injury Scale of the American Association for the Surgery of Trauma (grades I to V, with grade V being the worst possible injury). MAIN OUTCOME MEASURES: Failure of NOMSI, defined as the need for operation to the spleen after a period of nonoperative management. RESULTS: Compared with patients who had successful NOMSI, the 29 patients (52%) in whom NOMSI failed were older and more severely injured. They also required extra-abdominal operations more frequently, underwent transfusion with more units of blood while being managed nonoperatively, and had higher grades of splenic injury. Splenic injury grade III or higher and transfusion of more than 1 U of blood were identified as independent risk factors for failure of NOMSI. The existence of both risk factors predicted failure in 97% of cases. The grading by computed tomography correlated well with the actual injury to the spleen as seen at operation. CONCLUSIONS: In patients with high-grade splenic injuries who require a transfusion of more than 1 U of blood, NOMSI is very likely to fail. Decreasing the threshold for operation or intensifying the monitoring is highly recommended for such patients.

Adult↗

Mosaic analysis of GL2 gene expression and cell layer autonomy during the specification of Arabidopsis leaf trichomes.

Homozygous glabra2 (gl2) mutant Arabidopsis thaliana Landsberg erecta plants with only a few rudimentary single spiked trichomes on the leaf margin were transformed with a genomic clone of GL2, resulting in partial restoration of the normal leaf trichome phenotype. The introduced GL2 transgene was configured as part of an FLP recombinase-responsive gene switch, which permitted visibly marked gl2 mutant clonal sectors to be generated by FLP recombinase-mediated deletion of the GL2 transgene with concomitant activation of a previously silent beta-glucuronidase (GUS) marker gene. GUS marked sectors extending through all three leaf cell layers (L1, L2, and L3) displayed the anticipated gl2 mutant phenotype, whereas immediately adjacent unmarked tissue, and unmarked tissues overlaying GUS sectors restricted to the L2 and/or L3 cell layers, retained the GL2 restored phenotype. These data support the view that the GL2 gene product acts in a region-autonomous manner within a single cell layer and indicate that GL2 gene expression in the L1 layer is sufficient for GL2-directed outgrowth of trichomes.

Arabidopsis↗